Activation of the IL-2 gene promoter by HTLV-I tax involves induction of NF-AT complexes bound to the CD28-responsive element

EMBO J. 1996 Jul 15;15(14):3744-50.


The tax gene product of the type I human T-cell leukemia virus (HTLV-I) is a potent transcriptional activator of various growth-related cellular genes, including that encoding interleukin-2 (IL-2). Tax activation of many of these target genes appears to be mediated by the NF-kappa B/Rel and CREB/ATF family of cellular transcription factors. However, the mechanism by which Tax transactivates the IL-2 gene remains unclear. In the present study, we demonstrate that neither NF-kappa B/Rel nor CREB/ATF is sufficient for Tax-mediated activation of the IL-2 promoter. Two novel nuclear protein complexes are induced by Tax and specifically bind to an IL-2 gene enhancer, the CD28-responsive element (CD28RE). Immunobiochemical analyses suggest that these DNA binding complexes contain at least two members of the nuclear factor of activated T cells, NF-ATp and NF-ATc. However, the CD28 binding NF-AT complexes do not contain Jun and Fos family proteins that have been proposed to serve as NF-AT partners in the activation of the IL-2 NF-AT motif. Transient transfection studies demonstrate that the in vivo expressed NF-ATp binds to the CD28RE probe and enhances Tax-mediated activation of this critical IL-2 enhancer. We demonstrate further that binding of NF-AT to CD28RE is critical for Tax activation of the IL-2 promoter. Together, these results suggest a novel mechanism of Tax-mediated activation of the IL-2 gene, which involves the induction of NF-AT-containing CD28RE binding complexes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activating Transcription Factors
  • Animals
  • Base Sequence
  • Binding Sites
  • Blood Proteins / metabolism
  • CD28 Antigens* / metabolism
  • Cell Line
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA Probes
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Enhancer Elements, Genetic
  • Gene Products, tax / physiology*
  • Human T-lymphotropic virus 1 / physiology*
  • Humans
  • Interleukin-2 / genetics*
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Promoter Regions, Genetic*
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism
  • Signal Transduction
  • Transcription Factor RelB
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured


  • Activating Transcription Factors
  • Blood Proteins
  • CD28 Antigens
  • Cyclic AMP Response Element-Binding Protein
  • DNA Probes
  • DNA-Binding Proteins
  • Gene Products, tax
  • Interleukin-2
  • NF-kappa B
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • RELB protein, human
  • Relb protein, mouse
  • Transcription Factors
  • Transcription Factor RelB